Evidence map›Paper›PMID 22728933›Full record

ArticleThe Journal of clinical investigation2012

Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition.

Hiroyuki Mori, Tyler C Prestwich, Michael A Reid, Kenneth A Longo, Isabelle Gerin, William P Cawthorn, Vedrana S Susulic, Venkatesh Krishnan, Andy Greenfield, Ormond A Macdougald

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 1 pooled it
7.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

97 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Review
  6. Article
  7. Review
  8. Regulation of Stem Cell Function by NADPhysiology (Bethesda, Md.) · 2025
    Review
  9. Regulatory effect of Wnt signaling on mitochondria in cancer: from mechanism to therapy.Apoptosis : an international journal on programmed cell death · 2025
    Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Adipokines in atherosclerosis: unraveling complex roles.Frontiers in cardiovascular medicine · 2023
    Review
  18. Article
  19. Review
  20. Article

37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 3 countries.

Hiroyuki MoriDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Tyler C Prestwich
Michael A Reid
Kenneth A Longo
Isabelle Gerin
William P Cawthorn
Vedrana S Susulic
Venkatesh Krishnan
Andy Greenfield
Ormond A Macdougald
University of Michigan · USDiabetes Australia · AUEli Lilly (United States) · USMedical Research Council · GBProteostasis Therapeutics (United States) · US

Funding

PUBLIC HEALTH DEMONSTRATIONP60DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MYERS, MARTIN G · 1985 to 2012
$26.5M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID P OLSON · 2013 to 2026
$24.3M
Pilot and Feasibility (P and F) ProgramP30DK089503 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joyce Lee · 2010 to 2026
$20.3M
CELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8M
SYTEMS AND INTEGRATIVE BIOLOGYT32GM008322 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOW, MALCOLM JAMES · 1990 to 2020
$5.7M
Roles for Wnt Signaling in Adipose TissueR01DK062876 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MACDOUGALD, ORMOND A · 2003 to 2018
$5.1M
Regulation of adipocyte differentiation and metabolismR01DK051563 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MACDOUGALD, ORMOND A · 1996 to 2010
$3.2M
Roles for Wnt signaling in adipose tissueR56DK062876 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MACDOUGALD, ORMOND A · 2008 to 2008
$225k
Medical Research Council MC_U142684167NIDDK NIH HHS DK089503NIDDK NIH HHS DK51563NIDDK NIH HHS N02 DK062876NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK089503NIDDK NIH HHS P60 DK020572NIDDK NIH HHS P60DK020572NIDDK NIH HHS R01 DK051563NIDDK NIH HHS R01 DK062876NIGMS NIH HHS T32 GM007315NIGMS NIH HHS T32 GM008322
6 · The paper itself

Abstract

Preadipocytes secrete several WNT family proteins that act through autocrine/paracrine mechanisms to inhibit adipogenesis. The activity of WNT ligands is often decreased by secreted frizzled-related proteins (SFRPs). Sfrp5 is strongly induced during adipocyte differentiation and increases in adipocytes during obesity, presumably to counteract WNT signaling. We tested the hypothesis that obesity-induced Sfrp5 expression promotes the development of new adipocytes by inhibiting endogenous suppressors of adipogenesis. As predicted, mice that lack functional SFRP5 were resistant to diet-induced obesity. However, counter to our hypothesis, we found that adipose tissue of SFRP5-deficient mice had similar numbers of adipocytes, but a reduction in large adipocytes. Transplantation of adipose tissue from SFRP5-deficient mice into leptin receptor-deficient mice indicated that the effects of SFRP5 deficiency are tissue-autonomous. Mitochondrial gene expression was increased in adipose tissue and cultured adipocytes from SFRP5-deficient mice. In adipocytes, lack of SFRP5 stimulated oxidative capacity through increased mitochondrial activity, which was mediated in part by PGC1α and mitochondrial transcription factor A. WNT3a also increased oxygen consumption and the expression of mitochondrial genes. Thus, our findings support a model of adipogenesis in which SFRP5 inhibits WNT signaling to suppress oxidative metabolism and stimulate adipocyte growth during obesity.

Indexed as

Wnt Signaling Pathway3T3-L1 CellsAdaptor Proteins, Signal TransducingAdipocytesAdipogenesisAdipose Tissue, WhiteAnimalsCell EnlargementCells, CulturedEar, ExternalEnergy MetabolismExtracellular MatrixFemaleGlucoseInsulin ResistanceIntercellular Signaling Peptides and ProteinsAdaptor Proteins, Signal TransducingGlucoseIntercellular Signaling Peptides and ProteinsLeptinRNA, MessengerSecreted Frizzled-Related ProteinsSfrp5 protein, mouseWnt3A ProteinWnt3a protein, mouse

Identifiers

PMID22728933
PMCPMC3386832
OpenAlexW2060735685

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.